A research program will be undertaken by the applicant, Lorraine Kyne, MD, MPH in the Division of Gerontology at the Beth Israel Deaconess Medical Center (BIDMC). The award will provide five years of mentored training and research enabling her to develop her potential to become an independent clinical investigator focusing on patient-oriented research. Dr Jeanne Y. Wei, Chief of Gerontology at BIDMC, Director of the Division on Aging at Harvard Medical School and Dr. Ciaran P. Kelly, Associate Physician in the Division of Gastroenterology, BIDMC, will serve as mentors. The research component will focus on an important iatrogenic, nosocomial condition which affects predominantly older patients: Clostridium difficile-associated disease (CDAD). As the conventional antibiotic therapy of this condition is associated with a high relapse rate and the emergence of antimicrobial resistance, the long term goals of this project are to develop immunobiological products to prevent or ameliorate disease due to C. difficile and to test their efficacy in intervention studies in 'high risk' older persons. The specific aims of this project are; 1) to identify surrogate markers of immune protection against severe, prolonged or recurrent C. difficile diarrhea for use in future C. difficile active or passive immunization trials; 2) to explore the inter- relationship between the immune response to C. difficile, disease due to C. difficile and aging; and 3) to determine the clinical correlates of CDAD, in order to develop a clinical prediction rule which may be used to identify high risk individuals who may benefit from immunization or other preventative strategies. In addition to this project and scheduled meetings with Drs. Wei and Kelly, this award will include a formal research curriculum, including 1) Research ethics, 2) Clinical epidemiology, 3) Statistical analysis, 4) Clinical trials, 5) Aging research and 5) Laboratory techniques. The very substantial research, educational, and clinical resources of the Harvard Division on Aging and the BIDMC Gerontology and Gastroenterology Divisions will be committed to the applicant to ensure successful attainment of the goals of this award.